The objective of this project is the elucidation of the mechanisms which control transcription in eucaryotic cells. These studies are to serve as a basis for addressing the mechanisms operating in the development and onset of malignancy in human cells. We propose to define the organization of that area of the genome responsible for a known set of biochemical functions (the allantoin, arginine and ammonia degradative systems) and ascertain how the transcription of those genes are controlled. We have recently shown in Saccharomyces cerevisiae that: (1) allantoin is degraded in 5 steps to NH3 and CO2, (2) allophanic acid is the inducer for the synthesis of at least three of the allantoin degradative enzymes, and (3) the genes for these five enzymes appear to be organized in two unlinked clusters. The control of synthesis of at least three enzymes in separate areas of the genome by one small molecule almost certainly requires that its action be mediated by a protein control element. Therefore, we plan to: (1) define the linkage relationships of the structural and control genes responsible for synthesis of the allantoin, arginine and ammonia degradative enzymes and determine whether or not the genes that are linked to one another are also contiguous, (2) determine genetically if the synthesis of these enzymes is regulated by a protein control element acting in conjunction with allophanic acid, (3) purify the protein control element if the genetic experiments confirm its existence, (4) determine whether or not the first three enzymes of allantoin degradation are organized as a multienzyme complex, (5) establish the nature of the inducer of allantoicase and ureidoglycolase. (6) establish the reactions involved in the metabolism of oxaluric acid, (7) identify the reactions responsible for the conversion of ammonia to glutamate, and (8) isolate ammonia permease mutants in order to study the mechanism of ammonia uptake and its effects upon the control of nitrogen metabolism.